DESCRIPTION (Applicant's abstract): Nacelle's overall objective is to develop and commercialize a superior cystic fibrosis (CF) therapeutic, derived from a family of unique peptides that will form functional ion channels in defective cell membranes. Nacelle Therapeutics refers to this treatment modality as "Peptide-based channel replacement therapy." It is anticipated that enhanced transmembrane ion flow will eliminate or reduce the incidence of inflammation, mucous formation, and infection, and will result in a greatly diminished need for the currently employed anti-inflammatory and anti-infective products. The need for airway clearance therapies will also be diminished. The specific goal of the Phase I R/R&D is to evaluate the humoral effects or repeated exposure of mice to clinical dosages of both the all L- or D-isoforms of a lead Nacelle CF therapeutic channel-forming peptide. The treated mice will then be evaluated for peptide induced immunological or inflammatory responses. Specific evaluations in Phase I include physical, electrophysiological, and biological testing for effective dosage of the test compounds in the CF mouse model as well as for immunogenicity and activation of the inflammatory response in epithelium and alveolar macrophage of wild type mice and cultured cells. PROPOSED COMMERCIAL APPLICATION: Success will result in a widely used CF therapeutic. Since defective ion channels are becoming increasingly implicated in a variety of human diseases (episodic ataxia, diabetes, epilepsy, and Alzheimer's dementia), the basic technology may have much broader impact. Non-medical, modified-membrane applications in ion exchange and batteries may also be achievable.